WSU ESRP 531 - Fundamentals of Environmental Toxicology

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ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect 24 Biomar_Res.doc Page 1 of 25 November 28, 2005 Lecture 24: Biomarkers; Environmental and Tissue Contaminant Residues I. Biomarkers A. Biomarkers are biochemical, physiological, or histological indicators of either exposure to or effects of contaminants (or even natural products) at the suborganismal or organismal level of organization. 1. Biomarkers would be indicative of a contaminant effect or an exposure at the individual level. 2. However, biomarker quantification can be used to compare populations living in polluted vs. “pristine” sites to gain insight into potential exposure to toxic substances among populations. B. Biomarkers are generally measurements of sublethal effects in that living organisms are collected and assayed. However, some biomarkers can be reasonably hypothesized to be indicative of a type of contaminant, and thus biomarkers can be more specific measures of exposure. 1. One example of specificity is the use of acetylcholinesterase (AChE) activity, which can be inhibited by insecticides of the organophosphorus (OP) and carbamate (CB) classes; a. AChE can be measured in live or dead organisms (assuming they haven’t been deceased so long that the tissue and therefore the enzymes have decomposed). b. However, caution must be used because other compounds can inhibit AChE, including natural products (e.g., certain alkaloids) and heavy metals (e.g., copper). C. Types of biomarkers 1. Enzymes a. AChE—may be indicative of exposure to OP and CB insecticides 1. Inhibition can be tested by using a competitive inhibitor such as 2-Pam to reactivate the enzyme. b. ALAD (delta-aminolevulinic acid dehydratase): indicative of lead exposure c. ATPase d. Plant enzymes (peroxidase, RUBISCO) e. EROD Assay for cyt P4501A1 activity (ethoxyresorufin hydrolysis to resorufin) 1. Cyt P4501A1 is the microsomal oxidase isoforms induced by dioxins, PCBs, and PAHs 2. Energetics a. Adenylate energy charge b. Energy reserves c. Whole body Calorimetry d. Enzymes of intermediary metabolism e. Growth 3. Endocrine a. Hormone levelsES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect 24 Biomar_Res.doc Page 2 of 25 1. Corticosteroids/catecholamines 2. Thyroid hormone 3. Estrogen/Testosterone 4. Insulin/Glucagon 5. Growth hormone b. Protein synthesis under endocrine control 1. Vitellogenin levels in male fish 4. Blood chemistry 5. Growth Rate a. RNA and protein synthesis D. Limitations of biomarkers 1. Lack of specificity 2. Natural (endogenous) variability of response or variability of response as related to other environmental stressors a. As an example of variability among different populations, Olsen et al. (2001) ETAC 20:1725 showed that the biomarker enzymes, glutathione-s-transferase (GST) and acetylcholinesterase varied by factors of 1.84- and 1.81-fold, respectively, in Chironomus larvae held under ambient conditions of 13 “uncontaminated sites” (see Figure 1). Figure 1. Mean GST and AChE (mM/L/min/g protein) in whole body of Chironomus riparius larvae deployed in situ for 48 h at 13 uncontaminated river sites in the U.K. (Olsen et al., 2001, Environ. Toxicol. Chem. 20:1725-1732.)ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect 24 Biomar_Res.doc Page 3 of 25 3. For cold-blooded organisms, the temperature of the habitat during development may affect biomarker response. a. For example, Pacific tree frogs collected in California from comparatively warmer coastal sites have higher AChE activity when reared at 19°C (their normal habitat temperature) than when reared at 8°C (an average temperature characteristic of habitats in the Sierra Mts.) (Johnson et al. 2005, Environ. Toxicol. Chem. 24:2074-2077). Similar results were obtained for Pacific tree frogs collected in the Sierras (higher activity at warmer rearing temperatures). II. Analysis of Contaminant Residues: Issues in Environmental Analytical Chemistry A. Although biomarkers can be indicative of exposure, they are often not specific enough to determine the identity of a chemical and therefore are difficult to use to determine specific dosage (or concentration) to which an organism has been exposed. B. Measurement of contaminant residues both in the environment (which is useful for predicting exposure) and in tissues (which allows an estimation of what an organism has already been exposed to) is the most accurate and reliable way to estimate exposure. Thus, environmental analytical chemistry is the tool of choice for exposure estimation. 1. In addition to their importance in estimating exposure, residues of contaminants are monitored for compliance with various numerical standards. a. For example, under the Clean Water Act, EPA can promulgate guidelines known as ambient water quality criteria for the protection of aquatic biota. 1. These guidelines are not enforceable on the Federal level, but states can adopt similar guidelines that may be enforceable standards. 2. In some cases the standards, criteria, or guidelines for protection of aquatic biota are as low as 1 part per trillion (i.e., 1 ppt--applies to DDT residues) 2. Thus, knowing how residue numbers are produced and some of the issues related to detection and quantitation makes us a bit more skeptical and perhaps appreciative of the tremendous amount of residue monitoring that is presented in technical reports and the refereed scientific literature. C. The “Desperately Seeking Nothing” Syndrome 1. Capability of analyzing contaminants to levels of ppt and even below has evolved without a corresponding understanding of biological effects at these levels (Figure 2).ES/RP 531 Fundamentals of Environmental Toxicology Fall 2005 ESRP531 Lect 24 Biomar_Res.doc Page 4 of 25 10-310010-610-910-121950 1960 1970 1980 1990 2000ppthppmppbpptppq?10-15g / LYear Figure 2. Evolution of analytical capability. a. Bear in mind that requirements for toxicological testing only demand comparatively high dose testing; i.e., the doses where a biological effect is likely to be observed (although many contaminants will not produce a biological effect in chronic toxicity testing unless high doses relative to environmental concentrations are administered). 2. What does it mean to analyze something to the level of ppt? a. Significance of substance purity by percentage 1.


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